1-43736349-G-T

Variant names:

• chr1-43736349-G-T
• NM_006279.5:c.87G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006279.5(ST3GAL3):​c.87G>T​(p.Lys29Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K29K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST3GAL3 NM_006279.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

Genes affected

ST3GAL3 (HGNC:10866): (ST3 beta-galactoside alpha-2,3-sialyltransferase 3) The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Mutations in this gene have been associated with a form of autosomal recessive nonsymdromic cognitive disability as well as infantile epileptic encephalopathy. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ENSG00000284989 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38654795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL3	NM_006279.5	c.87G>T	p.Lys29Asn	missense_variant	Exon 2 of 12	ENST00000347631.8	NP_006270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.87G>T	p.Lys29Asn	missense_variant	Exon 2 of 12	5	NM_006279.5	ENSP00000317192.6
ENSG00000284989	ENST00000645057.1	n.*1409G>T		non_coding_transcript_exon_variant	Exon 16 of 26			ENSP00000494063.1
ENSG00000284989	ENST00000645057.1	n.*1409G>T		3_prime_UTR_variant	Exon 16 of 26			ENSP00000494063.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	.;D;D;D;D;T;D;T;D;D;D;D;T;D;D;.;T;D;D;D;T;T;D;D;T;D;T;T;T;D;.;D;.;.;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.1	M;M;M;M;M;M;M;.;.;.;M;.;M;M;M;M;.;M;.;.;.;M;.;.;M;M;M;M;M;M;M;M;M;M;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.6	N;N;N;D;D;N;N;.;.;.;N;.;N;.;N;.;.;N;.;N;.;.;N;.;D;D;N;N;N;N;D;N;D;N;.;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D;D;T;D;D;D;D;.;.;.;D;.;D;.;D;.;.;D;.;D;.;.;D;.;D;D;D;D;D;D;D;D;D;D;.;.
Sift4G	Uncertain	0.028	D;D;D;D;D;D;D;.;.;.;T;.;T;.;D;.;.;D;.;D;.;.;D;.;D;D;T;D;D;D;D;T;D;D;.;.
Polyphen		1.0	D;D;D;.;D;D;D;.;.;.;.;.;D;D;D;D;.;D;.;.;.;D;.;.;D;D;D;D;.;D;D;D;.;D;.;.
Vest4		0.69
MutPred		0.52		Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);Loss of ubiquitination at K29 (P = 0.0183);.;.;
MVP		0.58
MPC		1.7
ClinPred		0.99	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-44202020;